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Phase 3 trial assesses intraoperative radiotherapy for glioblastoma
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An international randomized phase 3 trial is underway to evaluate the efficacy of intraoperative radiotherapy for patients with glioblastoma multiforme.
Patients with glioblastoma typically undergo surgery — with the goal to remove as much of the tumor as can be done safely — followed by chemotherapy and radiation.
In the multicenter, open-label INTRAGO-II trial, investigators at multiple institutions will assess whether the addition of intraoperative radiotherapy (IORT) to standard treatment improves prevention of tumor regrowth.
Researchers will randomly assign 50% of study participants to IORT plus standard treatment. The other half of patients will receive standard therapy alone.
IORT already is incorporated into treatment protocols for several malignancies, such as breast, gynecologic, head and neck, pancreatic, colorectal and bone cancers.
“Despite chemotherapy and radiation treatment to the area where the tumor resides, the most frequent recurrence is in the resection bed,” Abhishek Solanki, MD, assistant professor and director of clinical research at Loyola University Chicago, one of the centers participating in the study, told HemOnc Today. “With intraoperative radiotherapy, a high dose of radiation is given to the resection bed. This can help allow for a higher dose to be administered more safely, because it is given directly to the cavity. It is also given at the time of surgery, so there is no period between the surgery and the start of radiation that allows for the cancer to recur in that area.”
University Medical Center Mannheim is the study sponsor. Frank Giordano, MD, interim chair of the department of radiation oncology at the medical center, is the trial’s principal investigator.
The current research builds on a prior phase 1/phase 2 trial that Giordano and colleagues conducted to investigate IORT to the resection cavity for 15 patients with newly diagnosed glioblastoma. The results, published earlier this year in Neurosurgery, showed the approach was feasible and associated with manageable toxicity.
The 15 patients were treated at three dose levels. Among them, 13 underwent incomplete resection and 12 received per-protocol treatment. Median follow-up was 13.8 months.
Investigators reports five cases of radionecrosis, two of which were grade 3. Other grade 3 events deemed related to external beam radiotherapy or IORT included one case each of wound dehiscence, cerebrospinal fluid leakage and cyst formation. No IORT-related deaths occurred.
Median PFS was 11.2 months for all patients and 11.3 months for those who received per-protocol treatment. Median OS was 16.2 months for all patients and 17.8 months for those who received per-protocol treatment.
The INTRAGO-II trial is designed to include 314 patients, 39 of whom are already enrolled. Enrollment should be completed by early 2021. Median PFS will be the primary endpoint, and researchers hypothesize they can achieve at least a 50% improvement with IORT.
“[The trial] enrolls patients suitable for gross or subtotal tumor resection, a population that is potentially able to achieve long-term survival,” Giordano told HemOnc Today. “However, microscopic residual tumors may regrow within a few months, even if a favorable molecular subtype is present. IORT to areas of residual disease may, thus, be beneficial for these patients.”
If the trial confirms the efficacy and safety of IORT, the procedure likely will be implemented in national and international guidelines as a part of routine clinical care for patients with resectable glioblastoma, Giordano said.
Safety concerns for the treatment modality include a potential increased risk for inflammation and damage to the surrounding brain tissue compared with standard chemotherapy and radiation. An increased risk for wound healing deficits or infections also is possible. However, based on observations from prior studies, these risks appear low, Solanki said. – by Joe Gramigna
For more information:
Abhishek Solanki, MD, can be reached at Loyola University Medical Center, 2160 S. First Ave., Maywood, IL 60153; email: abhishek.solanki@lumc.edu.
Frank Giordano, MD, can be reached at University Medical Center Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim, Germany D-68167; email: frank.giordano@umm.de.
Reference:
Giordano F, et al. Neurosurgery. 2018; doi:10.1093/neuros/nyy018.
Disclosures: Giordano reports grants or personal fees from AstraZeneca GmbH, Bristol-Myers Squibb, Carl Zeiss Meditec AG, Merck Sharp & Dohme GmbH, Noxxon Pharma AG and Roche. He also reports other relationships with Implacit GmbH and nonfinancial support from Oncare GmbH. Solanki reports travel fees from Carl Zeiss.